The disagreeable nature of itching--defined as far back as the 17th century as an unpleasant skin sensation that elicits the urge to scratch--is apparent to anyone who has wandered into a clump of poison ivy or experienced a mosquito bite. The identity of the central mediator of this "unpleasant sensation," however, has been unclear. Sun and Chen found that, in mice, a subset of unmyelinated dorsal root ganglion neurons expressed gastrin-releasing peptide (GRP) and that the GRP receptor (GRPR) was specifically localized to lamina I of the dorsal horn of the spinal cord (locations and neuron type consistent with a possible role in mediating itch perception). Mutant mice lacking the GRPR showed responses to heat and pain that were comparable to those of wild-type mice, but they displayed an attenuated scratching response to various histamine-dependent and -independent pruritogenic stimuli. Injection of a GRPR agonist into the cerebrospinal fluid of wild-type mice elicited scratching, whereas injection of a GRPR antagonist inhibited scratching in response to pruritogenic stimuli. Thus, the authors conclude that, at the level of the spinal cord, the GRPR is a mediator of an itch-specific signaling pathway--information that may provide an avenue toward the effective therapy of chronic and intractable pruritis.